Guldagerdobson7017
Vancomycin (VCM) is a glycopeptide antibiotic widely used to treat serious infections caused by methicillin-resistant Staphylococcus aureus and has been associated with some severe side effects such as hepatotoxicity and nephrotoxicity. However, the underlying mechanism of VCM-induced hepatotoxicity is not yet fully understood. Therefore, the current study was designed to evaluate the protective effects of zingerone (Zin) against VCM-induced hepatotoxicity in rats.
VCM was intraperitoneally administered at a dose of 200mg/kg body weight (b.w.) for 7days alone and in combination with the orally administered Zin (25 and 50mg/kg b.w).
Zin treatment significantly improved VCM-induced hepatic lipid peroxidation, glutathione depletion, reduced antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities and liver function markers (aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase). Histopathological integrity and immunohistochemical expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the VCM-induced liver tissue were ameliorated after Zin administration. In addition, Zin reversed the changes in levels and/or activities of inflammatory and apoptotic parameters such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p53, cysteine aspartate specific protease-3 (caspase-3), cysteine aspartate specific protease-8 (caspase-8), cytochrome c, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) in the VCM-induced hepatotoxicity.
Collectively, these results reveal probable ameliorative role of Zin against VCM-induced hepatotoxicity.
Collectively, these results reveal probable ameliorative role of Zin against VCM-induced hepatotoxicity.
The purpose of this paper is to unearth the ceRNA regulatory mechanism of SNHG7 in bladder cancer (BCa).
The expression of SNHG7 in BCa cells was uncovered by qRT-PCR. The biological functions of SNHG7 in BCa cells were explored by CCK-8 assay, colony formation assay, flow cytometry analysis, wound healing assay and transwell assay. Luciferase reporter assay and RIP assay were applied to analyze the interaction of ELK1 with SNHG7 or miR-2682-5p.
SNHG7 was conspicuously highly expressed in BCa tissues and cells. The upregulated expression of SNHG7 was related with poor prognosis in BCa patients. Moreover, SNHG7 exerted oncogenic functions in BCa through enhancing cell growth, migration and invasion. ELK1 increased the level of SNHG7 by binding with the promoter region of SNHG7. SNHG7 strengthened the expression of ELK1 via acting as a sponge of miR-2682-5p. Both ELK1 and miR-2682-5p involved in the SNHG7-mediated BCa progression.
ELK1/SNHG7/miR-2682-5p feedback loop enhances cell growth, migration and invasion in BCa.
ELK1/SNHG7/miR-2682-5p feedback loop enhances cell growth, migration and invasion in BCa.
Endoplasmic reticulum stress (ERS) as an emerging factor is involved in insulin resistance (IR), which is the pathological basis of diabetes mellitus. Accumulation of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase is associated with IR, but the underlying mechanisms have not been elucidated. This study was to reveal the important role of ADMA in IR and determine whether endogenous ADMA accumulation contributes to hepatic IR via ERS in diabetic rats and hepatocytes.
Diabetic rat model was induced by a single intraperitoneal injection of streptozotocin (50mg/kg). Phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (Akt) was detected to evaluate IR. The protein kinase PKR-like ER kinase (PERK) and eukaryotic initiation factor 2α kinase (eIF2α) phosphorylation, x-box binding protein-1 (XBP-1) splicing, glucose-regulated protein 78 (GRP78) and C/EBP homologues protein (CHOP) expressions were measured to assess ERS.
Endogenous ADMA content was significantly increased and positively correlated with either IR as evidenced by increased IRS1 at serine and reduced Akt phosphorylation or ERS as indicated by upregulations of PERK and eIF2α phosphorylation, XBP-1 splicing, GRP78 and CHOP expressions in the liver of diabetic rats compared with control rats. Exogenous ADMA directly caused IR and ERS in dose- and time-dependent manners in primary mouse hepatocytes. Pretreatment with ERS inhibitor 4-phenylbutyrate or ADMA antagonist L-arginine not only improved ADMA-associated or -induced hepatic IR but also attenuated ADMA-associated or -induced ERS in diabetic rats or hepatocytes.
These findings indicate that endogenous ADMA accumulation contributes to hepatic IR via ERS in diabetic rats.
These findings indicate that endogenous ADMA accumulation contributes to hepatic IR via ERS in diabetic rats.
The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8+ T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue.
BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysist IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer.
Pathological cardiac hypertrophy (CH) is one of the main risk factors for heart failure and cardiac death. Mitochondrial dysfunction and oxidative stress often occur in hypertrophic cardiomyocytes. It was recently proposed that deficiency or decreased activity of glucose-6-phosphate dehydrogenase (G6PD) may be related to the development of CH. This study aimed to investigate the expression of G6PD in CH and its regulatory role in mitochondrial dysfunction and oxidative stress of CH cells.
Phenylephrine (PE) was used to create an in vitro model of CH. Using RT-qPCR and western blotting, the expression levels of target mRNAs and proteins were measured. ELISA assays and commercial kits based on spectrophotometry or colorimetry were used to measure mitochondrial function and oxidative stress. TargetScan and luciferase reporter gene assays were utilized for combination prediction and validation. CCK-8 and TUNEL kit were used to determine cell viability and apoptosis.
The results showed that G6PD overexpression attenuated the decreases of mitochondrial respiration, ATP, ATP synthetase and mitochondrial membrane potential induced by PE, as well as the increases of LDH release and apoptosis. Besides, PE elevated ROS activity, NO and MDA contents, and reduced SOD, CAT levels and cell viability. These effects were hindered by G6PD overexpression. MiR-24 was found to directly bind to G6PD at the motif of CUGAGCC and regulated its expression, furtherly, influenced the G6PD-mediated mitochondrial dysfunction and oxidative stress of CH cells.
Generally, our study demonstrated that miR-24/G6PD regulates mitochondrial dysfunction and oxidative stress in CH cells, representing a new sight for CH therapy.
Generally, our study demonstrated that miR-24/G6PD regulates mitochondrial dysfunction and oxidative stress in CH cells, representing a new sight for CH therapy.
The aim of this study was to investigate the mechanism of pro-inflammatory phenotype transformation of microglia induced by oxygen-glucose deprivation (OGD), and how salvianolate regulates the polarization of microglia to exert neuroprotective effects.
The immunofluorescence and western blot experiments were used to verify the injury effect on neuronal cells after inflammatory polarization of microglia. Secondly, immunofluorescence staining and western blot were analyzed inflammatory phenotype of microglia and TLR4 signaling pathway after salvianolate treatment. RT-qPCR and ELISA assays were showed the levels of RNA and proteins of inflammatory factors in microglia. Finally, flow cytometry and western blot assay proved that salvianolate had a certain protective effect on neuronal injury after inhibiting the phenotype of microglia.
The OGD condition could promote inflammation and activate of TLR4 signal pathway in microglia, and the polarization of microglia triggered caspase-3 signal pathway of neuronal cell. The optimal concentrations of salvianolate were incubated with microglia under OGD condition, which could reduce the reactive oxygen species (ROS) expression (P=0.002) and also regulate the activity of SOD, CAT and GSH-px enzymes (P<0.05). Moreover, salvianolate treatment could inhibit TLR4 signal pathway (P=0.012), suppress the pro-inflammatory phenotype of microglia in OGD condition (P=0.018), and reduce the expression of IL-6 and TNF-α (P<0.05). Finally, neuronal damage induced by microglia under OGD condition was reversed after administration of the microglia supernatant after salvianolate treatment.
Salvianolate, as an antioxidant, plays a neuroprotective role by inhibiting the pro-inflammatory phenotype and decreasing the expression of ROS in microglia.
Salvianolate, as an antioxidant, plays a neuroprotective role by inhibiting the pro-inflammatory phenotype and decreasing the expression of ROS in microglia.The endothelium is the innermost vascular lining performing significant roles all over the human body while maintaining the blood pressure at physiological levels. N-butyl-N-(4-hydroxybutyl) nitrosamine molecular weight Malfunction of endothelium is thus recognized as a biomarker linked with many vascular diseases including but not limited to atherosclerosis, hypertension and thrombosis. Alternatively, prevention of endothelial malfunctioning or regulating the functions of its associated physiological partners like endothelial nitric oxide synthase can prevent the associated vascular disorders which account for the highest death toll worldwide. While many anti-hypertensive drugs are available commercially, a comprehensive description of the key physiological roles of the endothelium and its regulation by endothelial nitric oxide synthase or vice versa is the need of the hour to understand its contribution in vascular homeostasis. This, in turn, will help in designing new therapeutics targeting endothelial nitric oxide synthase or its interacting partners present in the cellular pool. This review describes the central role of vascular endothelium in the regulation of endothelial nitric oxide synthase while outlining the emerging drug targets present in the vasculature with potential to treat vascular disorders including hypertension.Prostate cancer (PCa) is a deadly disease for men, and studies of all types of omics data are necessary to promote precision medicine. The maturity of sequencing technology, the improvements of computer processing power, and the progress achieved in omics analysis methods have improved research efficiency and saved research costs. The occurrence and development of PCa is due to multisystem and multilevel pathological changes. Although omics research at a single level is important, this approach often has limitations. In contrast, the combined analysis of multiple types of omics data can better analyze PCa changes as a whole, thus ensuring the validity of research results to the greatest extent. This paper introduces the applications of single omics in PCa and then summarizes research progress in the combined analysis of two or more types of omics data, so as to systematically and comprehensively analyze the necessity of combined analysis of multiple omics data in PCa.
